Despite high incidence of depression after stroke, few trials have investigated the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS). Here, we aimed to evaluate clinical benefit of delivering a higher dose of rTMS compared to previous stroke trials. Secondary aims were to document adverse effects and investigate the role of functional connectivity as a potential mechanism of clinical response to rTMS treatment.
Eleven chronic stroke survivors were recruited to a double-blind, Sham-controlled, randomised trial to investigate 10 sessions of high-frequency rTMS for depression. Clinical assessments were obtained at baseline, after treatment and a 1-month follow-up. Adverse events were documented at completion of the treatment. Resting electroencephalography recordings were performed at baseline and after treatment to estimate functional connectivity.
There were no differences in baseline characteristics between groups (all p ≥ 0.42). Beck Depression Inventory scores decreased for the Active rTMS group from baseline to 1-month follow-up (p = 0.04), but did not change for the Sham group at post-treatment or follow-up (p ≥ 0.17). Stronger theta frequency functional connectivity between the left frontal cortex and right parietal cortex was associated with lower baseline depression (r = − 0.71, p = 0.05). This network strength increased following Active rTMS, with change in connectivity associated with improvement in BDI scores (r = 0.98, p = 0.001). Adverse events were transient and minor and were not statistically different between groups (p ≥ 0.21).
Active rTMS significantly improved depression and was well tolerated. The mechanistic role of theta frequency functional connectivity appears worthy of further investigation.
The trial was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12619001303134) on September 23, 2019.
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Beck depression inventory—II
Dorsolateral prefrontal cortex
Debiased weighted phase lag index
First dorsal interosseous
Motor evoked potential
Patient health questionnaire-9
Partial least squares
Repetitive transcranial magnetic stimulation
Repetitive transcranial magnetic stimulation
Stroke self-efficacy questionnaire
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The authors would like to acknowledge Dr Tobias Loetscher for assistance during study design.
This research was funded by a Research Themes Investment Scheme—University of South Australia grant. BH was supported by National Health and Medical Research Council (NHMRC) fellowship (1125054).
Conflicts of interest
None of the authors have potential conflicts of interest to be disclosed.
This study was approved by the University of South Australia Human Research Ethics Committee (ID number 200697). The study conformed to the standards defined in the latest revision of the Declaration of Helsinki. All patients and controls signed a written informed consent.
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Hordacre, B., Comacchio, K., Williams, L. et al. Repetitive transcranial magnetic stimulation for post-stroke depression: a randomised trial with neurophysiological insight. J Neurol 268, 1474–1484 (2021). https://doi.org/10.1007/s00415-020-10315-6
- Repetitive transcranial magnetic stimulation